Abstract 5905: 3′, 4-Dihydroxyflavonol Reduces Infarct Size in a Porcine Acute Myocardial Infarction-Reperfusion Model
Background: 3′, 4′-Dihydroxyflavonol (DiOHF) reduces infarct size after myocardial infarction-reperfusion but it is not suitable for clinical use due to its poor water solubility. We tested the cardio protective actions of NP202, a novel water soluble analog that has similar antioxidant and dilator activity to DiOHF in a porcine acute myocardial infarction-reperfusion injury model.
Method: The left anterior descending coronary artery was occluded distal to the second diagonal branch for 30 minutes in 14 pigs. At 29 minutes after occlusion, NP202 (6.6mg/kg dissolved in 10ml of 0.1M sodium carbonate) (n=7) or 0.1M sodium carbonate (10ml) (n=7) was injected via the tip of balloon catheter over 1 minute. At 24 hours after occlusion, coronary angiography was performed and Evan’s Blue (1.0%) was injected into both coronary arteries, CKMB and Troponin I were measured. After sacrifice, the left ventricle was sliced into 6 –7 transverse sections and photographed under ultraviolet light, before and after incubation in 1% triphenyltetrazolium chloride. The infarction area and the area at risk (AAR), defined as the non-fluorescent area, were traced manually from projected slides. After computerized planimetry, the percentage of the area was multiplied by the weight of the slice.
Results: The AAR size was comparable in treated and control group (18.4±2.6 vs. 19.6±4.7, p=0.54), indicating that the initial ischemic injury did not differ between the groups. The infarction area was significantly lower in the treated group than in the control group (3.0±1.3 vs. 6.6±2.7%, p=0.008). Moreover, the ratio of infarction area to AAR was also significantly lower in the treated group than in the control group (16.5±8.4 vs. 33.2±8.7%, p=0.003). Although CKMB and Troponin I did not reach significant difference, there was a trend toward lower enzymes in the treated group (CKMB: 1.8±1.7 vs. 8.8±9.5, p=0.08, Troponin I: 25.7±39.7 vs. 38.3±29.1, p=0.51).
Conclusion: In conclusion, the results of our study suggest that NP202 reduces infarct size in a porcine model of acute myocardial infarction-reperfusion.